Osteogenic toxicity in childhood acute lymphoblastic leukemia

Bone mineral density (BMD) Our multi-center study in children treated according to the Dutch Childhood Oncology Group (DCOG)-ALL9 protocol showed a three-years cumulative incidence of fractures of 18%. BMD of ALL patients was lower than of healthy peers. The year after treatment discontinuation BMD recovered, but remained lower than in healthy children. Low BMD at diagnosis, rather than the treatment-related decline, determined fracture risk. These low BMD values were influenced by age, weight and the immunophenotype of the leukemia. Moreover, single nucleotide polymorphisms of the vitamin-D receptor gene and of the folate metabolism (MTHFR 677C>T and MTRR 66A>G) determined the low BMD at diagnosis. Our randomized trial investigating an exercise program to prevent BMD reduction during ALL treatment, demonstrated no beneficial effects on BMD and fracture risk, probably due to non-compliance of such long-term required program. Osteonecrosis Six percent of the ALL patients developed symptomatic osteonecrosis during/ shortly after treatment (DCOG-ALL9 protocol) and older age and female gender were risk factors. That older children with ALL are more prone to develop osteonecrosis may reflect age-related differences in dexamethasone-induced changes in the coagulation system. Finally, current literature provides insufficient evidence to advise any treatment option to reduce the morbidity of osteonecrosis. Prevention of osteonecrosis is feasible by discontinuous, instead of continuous, corticosteroid administration. Conclusion One out of five patients suffer from osteogenic toxicity during/ shortly after the treatment of childhood ALL. The results led to recommendations on screening and treatment of osteogenic toxicity for patients treated according to the DCOG-ALL11 protocol.

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